Liverpool HIV Interactions

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Potential Interaction

Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir-DF (EVG/c/FTC/TDF)

Vinblastine

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Vinblastine is metabolised by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by elvitegravir/cobicistat resulting in the potential for increased incidence of adverse events. There is a case report of a patient who developed neuropathies as a result of a potential interaction between vinblastine and cobicistat while receiving elvitegravir/cobicistat/emtricitabine/tenofovir-DF. Coadministration of vinblastine with protease inhibitors was independently associated with WHO grade III-IV neutropenia in a clinical cohort. For boosted PIs, an inverse correlation between dosage of ritonavir and mean nadir neutrophil count was found. If possible, consider switching to a non-CYP inhibiting or inducing regimen. If coadministration is necessary, use with caution and monitor closely for vinblastine induced toxicity and reduce vinblastine dose if necessary. No interaction is expected with emtricitabine and tenofovir-DF.

Description:

A case study was reported of a 46-year-old HIV positive woman who developed Hodgkin’s lymphoma and was initiated on ABVD chemotherapy (doxorubicin/bleomycin/vinblastine/dacarbazine, 46/18.6/11/700 mg, every two weeks). Due to concerns of a drug-drug interaction, her ART was switched from a regimen containing rilpivirine to elvitegravir/cobicistat/emtricitabine/tenofovir-DF (Stribild: 150/150/300/200 mg, once daily). After the first cycle, the patient reported paraesthesia of the legs and difficulty walking. After the third cycle she presented with sensory-motor lower and upper limbs peripheral neuropathy, which was confirmed by electromyogram. Vinblastine was stopped and replaced with 150 mg etoposide. Stribild was also stopped and replaced with ritonavir/abacavir/lamivudine/darunavir (100/600/300/800 mg, once daily). The neuropathies decreased after two weeks but persisted for a further six months. The authors hypothesise a drug-drug interaction occurred via inhibition of CYP3A4 by cobicistat, increasing vinblastine toxicity.

Cobicistat-vinblastine interaction and severe peripheral neuropathy. Bidon D, Bauler S, Venon MD et al. AIDS, 2015, 29(9): 1120-1.